Chemoenzymatic synthesis of sugar-related polyhydroxylated compounds, iminocyclitols and their derivatives as glycosidase inhibitors
Section 1 (Introduction) is a comprehensive review of the subjects discussed in this thesis: biocatalysis, aldolases and iminocyclitols. It contains a description of the application of dihydroxyacetone phosphate (DHAP) and dihydroxyacetone (DHA) utilizing aldolases to the chemoenzymatic synthesis of...
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| Format: | doctoral thesis |
| Status: | Published version |
| Publication Date: | 2013 |
| Country: | España |
| Institution: | CBUC, CESCA |
| Repository: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/113239 |
| Online Access: | http://hdl.handle.net/10803/113239 |
| Access Level: | Open access |
| Keyword: | Catàlisi Catálisis Catalysis Sucres Azúcares Sugars Aldolasa Fructose-bisphosphate aldolase Ciències Experimentals i Matemàtiques 547 |
| Summary: | Section 1 (Introduction) is a comprehensive review of the subjects discussed in this thesis: biocatalysis, aldolases and iminocyclitols. It contains a description of the application of dihydroxyacetone phosphate (DHAP) and dihydroxyacetone (DHA) utilizing aldolases to the chemoenzymatic synthesis of bioactive compounds and an introduction to the structure, biological activities and synthesis of iminocyclitols. Recent bibliographic references are included at the end of the section. Section 2 (Objectives) outlines the aims of this thesis. Section 3 (Results and discussion) describes the studies carried out in this thesis. Bibliographic references are included as an overview of previous results and to support our statements at the end of each chapter. - Section 3.1 deals with the application of D-fructose-6-phosphate aldolase in organic chemistry. It describes the chemoenzymatic preparation of polyhydroxylated compounds, sugars 1-deoxy-D-xylulose and 1-deoxy-D-ido-hept-2-ulose and iminocyclitols 1-deoxynojirimycin, 1-deoxymannojirimycin and N-alkylated derivatives, 1,4-dideoxy-1,4-imino-D-arabinitol and 1,4,5-trideoxy-1,4-imino-D-arabinitol. An unprecedented methodology, having as a key step a novel enzymatic aldol addition reactions catalyzed by D-fructose-6-phosphate aldolase, is presented. - Section 3.2 presents the cascade chemical-enzymatic synthesis of a collection of novel 1,4-dideoxy-1,4-imino-D- and -L-arabinitol (DAB and LAB) 2-aminomethyl derivatives including 2-oxopiperazine conjugates which have an interest as potential glycosidase inhibitors. - Section 3.3 describes the chemoenzymatic synthesis of novel polyhydroxylated pyrrolizidines of the family of casuarines by means of an asymmetric strategy based on cascade aldol additions catalyzed by dihydroxyacetone phosphate (DHAP) and dihydroxyacetone (DHA) aldolases. - Section 3.4 describes the methodology and results of the preliminary in vitro assays for glycosidases inhibition activity of some of the compounds synthetized during the course of this thesis. Section 4 (Experimental) describes the procedure for the experimental work carried out in this project. 1H and 13C NMR spectra can be found in the attached CD. |
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